PROJECT SUMMARY The most common cause of childhood blindness in the developed world is cortical blindness; asphyxial injury is a well-known cause of such long-term visual impairment. Hypoxic ischemic encephalopathy (HIE) is also caused by severe perinatal asphyxia, and long-term outcomes include motor, cognitive, and visual deficits, some of which may not be apparent in early infancy and all of which impact quality of life. Clinicians must determine within the first hours of life whether an infant has HIE in order to initiate time-dependent hypothermia treatment, the first line of intervention, although even with hypothermia, mortality rates and disability rates are still high. Neurological examinations have been the primary tool for diagnosis and follow up assessment. At approximately one week after birth, brain magnetic resonance imaging (MRI) is used to quantify brain injury and together with examinations is used to predict neurological outcomes. Tests for developmental prognostic information remain complex and limited, and even infants with mild MRI findings have a range of outcomes that are difficult to predict in many cases. There is a need for a simple bedside test to add meaningful information regarding eye and brain injury in these infants. The retina and optic nerve head (retina/ONH) are an extension of the diencephalon and are the entry into the visual pathway, which comprises over 25% of the brain. Within the central nervous system, the retina/ONH are the only structures amenable to optical imaging at the subcellular level with spectral domain optical coherence tomography (SD-OCT). To fill the gap in bedside tests of early asphyxial injury, this study proposes novel non-contact, bedside SD-OCT imaging of retina/ONH without pharmacologic dilation, to detect abnormalities in microanatomy that are either: a direct result of asphyxia, that develop from secondary reperfusion injury or neuroinflammation, or that develop from retrograde atrophy. Each type of injury is a potentially useful indicator of HIE severity and treatment response. This research builds upon findings from such eye imaging in a very small group of HIE infants in whom SD-OCT features included retinal injury. Those findings motivate the steps proposed here, to perform prospective imaging of HIE infants in two nurseries to test the hypotheses that capture and measurement of retinal/ONH abnormalities are achievable and reproducible, that there is a range of severity of abnormalities and that these are distinct from the normal population, are reflective of MRI brain injury scores, and change over time. The results of this study will provide clinicians and researchers with breakthrough reproducible methods for standardized bedside imaging and image analyses. By distinguishing SD-OCT-based, micro-anatomic imaging biomarkers for severity and duration of newborn retinal/ONH asphyxial injury, this study will transform future clinical research in HIE, asphyxia injury and in infants with other eye and brain diseases including retinopathy of prematurity, genetic diseases such as incontinentia pigmenti, and Zika-associated eye and brain injury.